Neural substrates of parallel devaluation-sensitive and devaluation-insensitive Pavlovian learning in humans.

We aim to differentiate the brain regions involved in the learning and encoding of Pavlovian associations sensitive to changes in outcome value from those that are not sensitive to such changes by combining a learning task with outcome devaluation, eye-tracking, and functional magnetic resonance imaging in humans. Contrary to theoretical expectation, voxels correlating with reward prediction errors in the ventral striatum and subgenual cingulate appear to be sensitive to devaluation. Moreover, regions encoding state prediction errors appear to be devaluation insensitive. We can also distinguish regions encoding predictions about outcome taste identity from predictions about expected spatial location. Regions encoding predictions about taste identity seem devaluation sensitive while those encoding predictions about an outcome's spatial location seem devaluation insensitive. These findings suggest the existence of multiple and distinct associative mechanisms in the brain and help identify putative neural correlates for the parallel expression of both devaluation sensitive and insensitive conditioned behaviors.

A randomized controlled trial investigating the effect of liraglutide on self-reported liking and neural responses to food stimuli in participants with obesity.

BACKGROUND/OBJECTIVES: Obesity is a complex condition and the mechanisms involved in weight gain and loss are not fully understood. Liraglutide, a GLP-1 receptor agonist, has been demonstrated to successfully promote weight loss in patients with obesity (OB). Yet, it is unclear whether the observed weight loss is driven by an alteration of food liking. Here we investigated the effects of liraglutide on food liking and the cerebral correlates of liking in OB. SUBJECTS/METHODS: This study was a randomized, single-center, double-blind, placebo-controlled, parallel group, prospective clinical trial. 73 participants with OB and without diabetes following a multidisciplinary weight loss program, were randomly assigned (1:1) to receive liraglutide 3.0 mg (37.40 ± 11.18 years old, BMI = 35.89 ± 3.01 kg) or a placebo (40.04 ± 14.10 years old, BMI = 34.88 ± 2.87 kg) subcutaneously once daily for 16 weeks. INTERVENTIONS/METHODS: We investigated liking during food consumption. Participants reported their hedonic experience while consuming a high-calorie food (milkshake) and a tasteless solution. The solutions were administered inside the scanner with a Magnetic Resonance Imaging (MRI)-compatible gustometer to assess neural responses during consumption. The same procedure was repeated during the pre- and post-intervention sessions. RESULTS: None of the effects involving the intervention factor reached significance when comparing liking between the pre- and post-intervention sessions or groups. Liking during food reward consumption was associated with the activation of the ventromedial prefrontal cortex (vmPFC) and the amygdala. The liraglutide group lost more weight (BMI post-pre = -3.19 ± 1.28 kg/m2) than the placebo group (BMI post-pre = -0.60 ± 1.26 kg/m2). CONCLUSIONS: These results suggest that liraglutide leads to weight loss without self-report or neural evidence supporting a concomitant reduction of food liking in participants with OB.

Neural substrates of parallel devaluation-sensitive and devaluation-insensitive Pavlovian learning in humans.

Pavlovian learning depends on multiple and parallel associations leading to distinct classes of conditioned responses that vary in their flexibility following changes in the value of an associated outcome. Here, we aimed to differentiate brain areas involved in learning and encoding associations that are sensitive to changes in the value of an outcome from those that are not sensitive to such changes. To address this question, we combined a Pavlovian learning task with outcome devaluation, eye-tracking and functional magnetic resonance imaging. We used computational modeling to identify brain regions involved in learning stimulus-reward associations and stimulus-stimulus associations, by testing for brain areas correlating with reward-prediction errors and state-prediction errors, respectively. We found that, contrary to theoretical predictions about reward prediction errors being exclusively model-free, voxels correlating with reward prediction errors in the ventral striatum and subgenual anterior cingulate cortex were sensitive to devaluation. On the other hand, brain areas correlating with state prediction errors were found to be devaluation insensitive. In a supplementary analysis, we distinguished brain regions encoding predictions about outcome taste identity from those involved in encoding predictions about its expected spatial location. A subset of regions involved in taste identity predictions were devaluation sensitive while those involved in encoding predictions about spatial location were devaluation insensitive. These findings provide insights into the role of multiple associative mechanisms in the brain in mediating Pavlovian conditioned behavior - illustrating how distinct neural pathways can in parallel produce both devaluation sensitive and devaluation insensitive behaviors.

Differential Contributions of Ventral Striatum Subregions to the Motivational and Hedonic Components of the Affective Processing of Reward.

The ventral striatum is implicated in the affective processing of reward, which can be divided into a motivational and a hedonic component. Here, we examined whether these two components rely on distinct neural substrates within the ventral striatum in humans (11 females and 13 males). We used a high-resolution fMRI protocol targeting the ventral striatum combined with a pavlovian-instrumental task and a hedonic reactivity task. Both tasks involved an olfactory reward, thereby allowing us to measure pavlovian-triggered motivation and sensory pleasure for the same reward within the same participants. Our findings show that different subregions of the ventral striatum are dissociable in their contributions to the motivational versus the hedonic component of the affective processing of reward. Parsing the neural mechanisms of the interplay between pavlovian incentive and hedonic processes may have important implications for understanding compulsive reward-seeking behaviors such as addiction, binge eating, or gambling.

Determining the effects of training duration on the behavioral expression of habitual control in humans: a multilaboratory investigation.

It has been suggested that there are two distinct and parallel mechanisms for controlling instrumental behavior in mammals: goal-directed actions and habits. To gain an understanding of how these two systems interact to control behavior, it is essential to characterize the mechanisms by which the balance between these systems is influenced by experience. Studies in rodents have shown that the amount of training governs the relative expression of these two systems: Behavior is goal-directed following moderate training, but the more extensively an instrumental action is trained, the more it becomes habitual. It is less clear whether humans exhibit similar training effects on the expression of goal-directed and habitual behavior, as human studies have reported contradictory findings. To tackle these contradictory findings, we formed a consortium, where four laboratories undertook a preregistered experimental induction of habits by manipulating the amount of training. There was no statistical evidence for a main effect of the amount of training on the formation and expression of habits. However, exploratory analyses suggest a moderating effect of the affective component of stress on the impact of training over habit expression. Participants who were lower in affective stress appeared to be initially goal-directed, but became habitual with increased training, whereas participants who were high in affective stress were already habitual even after moderate training, thereby manifesting insensitivity to overtraining effects. Our findings highlight the importance of the role of moderating variables such as individual differences in stress and anxiety when studying the experimental induction of habits in humans.

3D-Printed Pacifier-Shaped Mouthpiece for fMRI-Compatible Gustometers.

Gustometers have made it possible to deliver liquids in functional magnetic resonance imaging (fMRI) settings for decades, and mouthpieces are a critical part of these taste delivery systems. Here, we propose an innovative 3D-printed fMRI mouthpiece inspired by children's pacifiers, allowing human participants to swallow while lying down in an MRI scanner. We used a large sample to validate the effectiveness of our method. The results suggest that the mouthpiece can be used to deliver taste stimuli by showing significant clusters of activation in the insular and piriform cortex, which are regions that have been consistently identified in taste processing. This mouthpiece fulfills several criteria guaranteeing a gustatory stimulus of quality, making the delivery precise and reliable. Moreover, this new pacifier-shaped design is simple and cheap to manufacture, hygienic, comfortable to keep in the mouth, and flexible to use in diverse cases. We hope that this new method will promote and facilitate the study of taste and flavor perception in the context of reward processing in affective neuroscience, and thus, help provide an integrative approach to the study of the emotional nature of rewards.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.

Vulnerability to relapse under stress: insights from affective neuroscience.

In this review article, we aim at analysing the role of stress in addiction and relapse. In order to do so, we first offer a summary of the findings from affective neuroscience trying to understand compulsive reward-seeking behaviours. These behaviours are characterised by an imbalance between the considerable amount of effort an individual is willing to mobilise to obtain a reward and the comparatively little pleasure that is felt once the reward is obtained and consumed. We illustrate how the neuropsychological mechanisms underlying these behaviours might play an important role in substance addiction and in particular for stress-induced relapse. We then review evidence suggesting that a personalised health approach would be particularly beneficial in order to better understand the role of stress in addiction and relapse in humans. More specifically, observing individual differences during distinct forms of learning (Pavlovian, habitual and goal-directed learning) might represent a very promising way to identify risk profiles for compulsive reward-seeking behaviours, addiction, and vulnerabilities to relapse under stress.

Considerations for the study of "incentive hope" and sign-tracking behaviors in humans.

The amplification of reward-seeking behavior under uncertainty described by Anselme & Güntürkün is based on the animal literature. However, this phenomenon could provide valuable information for the understanding of several dysfunctional human behaviors such as overeating and gambling. Therefore, we formulated some considerations on how the "incentive hope" hypothesis could be tested on a human population.

Behavioural evidence for parallel outcome-sensitive and outcome-insensitive Pavlovian learning systems in humans.

There is a dichotomy in instrumental conditioning between goal-directed actions and habits that are distinguishable on the basis of their relative sensitivity to changes in outcome value. It is less clear whether a similar distinction applies in Pavlovian conditioning, where responses have been found to be predominantly outcome sensitive. To test for both devaluation insensitive and devaluation sensitive Pavlovian conditioning in humans, we conducted four experiments combining Pavlovian conditioning and outcome devaluation procedures while measuring multiple conditioned responses. Our results suggest that Pavlovian conditioning involves two distinct types of learning: one that learns the current value of the outcome which is sensitive to devaluation, and one that learns about the spatial localisation of the outcome which is insensitive to devaluation. Our findings have implications for the mechanistic understanding of Pavlovian conditioning and provide a more nuanced understanding of Pavlovian mechanisms that might contribute to a number of psychiatric disorders.